Eugene Smith was born in Wichita, Kansas. He took his first photographs at age 15 and shortly after began to sell them to newspapers. After studying with Helene Sanders at the New York Institute of Photography he started working for Newsweek magazine in 1937. He left a year later and was represented by Black Star agency. He went on to join Life magazine (1939-1942) and Parade magazine.

Smith spent substantial time in the South Pacific: first for Flying magazine, covering the World War II (1943-1944) and a year later for Life magazine. He suffered severe injuries from shellfire whilst photographing there and for two years thereafter had to undergo medical operations.

Following recuperation Smith worked for Life magazine again (1947-1955) before resigning in order to join Magnum as an associate. With the support of two Guggenheim fellowships, he began a project in 1956 to photograph Pittsburgh, and made color photographs for the American Institute of Architects Centennial Exhibition at the National Gallery of Art in Washington, D.C. In 1957 he became a full member of Magnum. A year later he began a photographic essay on on a mental helath clinic in Haiti.

Smith resigned from Magnum in 1959, changing his status to contributing photographer. For one year (1961-1962) he photographed the Japanese industrial firm Hitachi Ltd. With Carole Thomas he worked to develop a magazine that was never published (1964-1965). In 1970 a retrospective exhibition "Let Truth Be the Prejudice", opened at the Jewish Museum, New York. The following year he moved to Minamata, Japan to document with Aileen Mioko Smith the aftermath of industrial pollution.

After moving back to Tucson, USA to teach at the university of Arizona, Smith died a year later from a stroke. His archives are kept at the Center for Creative Photography in Tucson, Arizona.